Is PEX2 p.Trp65fs (c.188dup) pathogenic?

PEX2 p.Trp65fs (c.188dup) is classified Likely pathogenic in PEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-28). No gnomAD frequency available for this variant; Associated with peroxisome biogenesis disorder 5A (Zellweger).

What condition is associated with PEX2 p.Trp65fs (c.188dup)?

PEX2 p.Trp65fs (c.188dup) is associated with peroxisome biogenesis disorder 5A (Zellweger) (ClinVar).

How common is PEX2 p.Trp65fs (c.188dup) in the general population?

PEX2 p.Trp65fs (c.188dup) is no gnomAD frequency available for this variant (gnomAD).

PEX2 p.Trp65fs

c.188dup · rs2487453279 · VCV2677679

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

peroxisome biogenesis disorder 5A (Zellweger)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.8	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEX2
Protein: p.Trp65fs
Coding: c.188dup
MANE Select: NM_000318
dbSNP: rs2487453279
Type: Duplication
Location: chr8:76983990 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 65: a UniProt-annotated variant site (in pbd5a)

Full PEX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 5A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX2 p.Trp65Cys Uncertain significance ★★ ⚠ same residue
PEX2 p.Cys109fs Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Pro209fs Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Pro91_Asn92insTer Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Ala74fs Pathogenic ★ same condition
PEX2 p.Cys247fs Likely pathogenic ★ same condition
PEX2 p.Glu6fs Pathogenic ★ same condition
PEX2 p.Gly133fs Pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pex2-p-trp65fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown